Combined Anti-IL 6 and Anti-VEGF Therapy for Diabetic Macular Edema

IL-6 is a cytokine, a pro-inflammatory cytokine.

And it actually signals through coupling with a membrane-bound protein on vascular endothelial cells called GP130.

And it leads to a whole, through the JAK-STAT pathway, a whole pro-inflammatory cascade leading to recruitment of other cytokines, inflammation, vascular permeability.

and has been strongly implicated in not just uveitic macular edema.

Obviously, we know that's inflammatory, but diabetic macular edema as well.

And we know this from the vitreous and aqueous humor samples of patients with DME versus matched controls, for example, those with DR but without DME.

or those without diabetes at all.

So we've got really good kind of a scientific basis for why targeting IL-6 might be helpful.

And then I think we all know that although anti-VEGF therapy is amazing and is a huge breakthrough for patients with DME, we also know that, you know, depending on who you ask, about a third of patients are what we might call suboptimal responders.

And it suggests that, hey, perhaps in those patients, something in addition to VEGF inhibition might be helpful.

And that's really what I was able to share at at um at arvo which is a molecule called the micabart this is a monoclonal antibody that targets il-6 it actually blocks il-6 signaling uh both the cis and trans signaling um which whatever we don't have to get into that part of it but the trans signaling is probably more what's relevant in the uh in the retina and retinal vascular diseases And there were two studies, but Micobart's being developed by Genentech Roche.

They've already read out a whole phase three program in uveitic macular edema.

And I believe they're submitting that for FDA regulatory approval for UME.

And this was a phase two program looking at... either in isolation, just IL-6 inhibition in DME.

That was a study called Alluvium that Arshad Kanani presented in the talk right before mine at Arvo.

And then I presented the Bardenas data, which was the Micobart plus 0.5 milligram ranibizumab in combination for patients with diabetic macular edema.

And so this was like, what can happen? What can we achieve if we use both agents together?

IL-6 is a cytokine, a pro-inflammatory cytokine.

And it actually signals through coupling with a membrane-bound protein on vascular endothelial cells called GP130.

And it leads to a whole, through the JAK-STAT pathway, a whole pro-inflammatory cascade leading to recruitment of other cytokines, inflammation, vascular permeability.

and has been strongly implicated in not just uveitic macular edema.

Obviously, we know that's inflammatory, but diabetic macular edema as well.

And we know this from the vitreous and aqueous humor samples of patients with DME versus matched controls, for example, those with DR but without DME.

or those without diabetes at all.

So we've got really good kind of a scientific basis for why targeting IL-6 might be helpful.

And then I think we all know that although anti-VEGF therapy is amazing and is a huge breakthrough for patients with DME, we also know that, you know, depending on who you ask, about a third of patients are what we might call suboptimal responders.

And it suggests that, hey, perhaps in those patients, something in addition to VEGF inhibition might be helpful.

And that's really what I was able to share at at um at arvo which is a molecule called the micabart this is a monoclonal antibody that targets il-6 it actually blocks il-6 signaling uh both the cis and trans signaling um which whatever we don't have to get into that part of it but the trans signaling is probably more what's relevant in the uh in the retina and retinal vascular diseases And there were two studies, but Micobart's being developed by Genentech Roche.

They've already read out a whole phase three program in uveitic macular edema.

And I believe they're submitting that for FDA regulatory approval for UME.

And this was a phase two program looking at... either in isolation, just IL-6 inhibition in DME.

That was a study called Alluvium that Arshad Kanani presented in the talk right before mine at Arvo.

And then I presented the Bardenas data, which was the Micobart plus 0.5 milligram ranibizumab in combination for patients with diabetic macular edema.

And so this was like, what can happen? What can we achieve if we use both agents together?